Contemporary medicine employs devices substituting the kidney function either for intermittent treatment, where the patient is connected with the device periodically in seances lasting several hours, or continuously, where the patient is connected with the device permanently. In either case there must be prevented blood coagulation in the capillary channels of the device filter and in other extracorporeal parts of the blood circuit. Usually in these cases the coagulation of blood is prevented by systemic supply of anticoagulation drugs which is accompanied with some hazard especially in patients with complex disorders. As alternatives there are sometimes employed: regional anticoagulation, adding anticoagulants, usually sodium citrate, then minimum systemic anticoagulation (using heparin and/or prostaglandins), or we get without of any anticoagulant and only flush the system with saline in regular intervals. No of the above said procedures is satisfactory and all are connected with some hazard for the patient, as e. g. metabolism alteration, bleeding or inadequate anticoagulation. In addition, improper anticoagulation measures, even when it does not cause instantaneous coagulation in the device circuitry, it can activate the cascades of coagulation steps and so alter the fragile and often just changed coagulation equilibrium. There must also be considered useless elevation of the cost of extracorporeal blood cleansing by frequent exchanges of sets and filters.
It is known that decrease of blood temperature inhibits enzymatic reactions in the coagulation cascade and deactivates primary hemostasis and also the coagulation process itself, as described e. g. in Rohrer M J, Natale A M, Crit Care Med, 1992 October; 20 (10): 1402-5.
In sufficiently low temperature the blood may become completely unable to coagulate. Hence appears the not yet tried possibility to employ cooling as an anticoagulation agent. The blood which left the patient body is first cooled and only thereafter it is led into the device substituting the kidney function and on the output of the device the blood is warmed up and led in the patient body.
This coagulation preventing method has just been tried successfully in experiments in animals—in pigs a three hours intermittent dialysis was applied where the blood in the circuit was cooled on 20° C. and before the return in the body it was rewarmed on 37° C. No traces of hemolysis could be observed which could be theoretically caused by sudden temperature changes (Otte K E et all., Blood Purif. 1997, 15: 200-207). But this research mainly tried to influence the compatibility between extracorporeal blood flow and life and observed only if the extracorporeal ways remained passable but did not examine in them any changes of blood coagulation or inactivation of coagulation and fibrinolytic processes. In addition, these authors followed the effectiveness of this method in intermittent extracorporeal method only, but not in the continuous one, in which the coagulation might be more apparent. Also the technical realization of the device was different; the blood was not cooled directly but only by the contact with the dialytic solution after its passage through a hose submerged in a vessel containing ice and water. For warming up served a microwave oven. Automatic control of the process was not tried here and the process did not fulfill even the most basic security parameters which could make possible to consider its clinical application for patients.
In blood passing through the device substituting the kidney function substances are exchanged between blood and dialytic solution over the semipermeable membrane, controlled by physical laws of the diffusion process. It is known that diffusion through a membrane is temperature dependent so that the temperature rise raises amounts of substances transported by diffusion. The EP1261413A1 patent uses this phenomenon letting the blood to pass two dialytic filters. In the first one the dialytic solution temperature is raised and the dialysis takes place under elevated temperature. In the second one the dialytic solution temperature is again decreased and hence the blood is cooled to the body temperature. The question is, if temperature rise above the normal body temperature in the first filter will not increase the activity of the coagulation processes in the circulating blood. The essence of the presented solution is reversed effect on the blood, i.e., its cooling prior to the input into the device substituting the kidneys. Because of the temperature dependence of diffusion rate—see above—we can anticipate that the dialysis in this arrangement could be less efficient. But this disadvantage cannot be considered too relevant, esp. in the regimen of continuous treatment, where there is the blood mainly filtered, i.e. certain volume of plasma is removed and is replaced by the substituting solution. The dialysis proper is minimum involved.
Blood temperature is often manipulated in heart surgery, in surgery employing extracorporeal circulation, where the cooling of the patient's body renders the operations on open heart technically possible. The aimed body temperature, to which is the patient cooled, is different depending on surgery type with the bottom temperature limit 16 to 17° C. For the cooling and reheating of the patient are used filters which in more modern devices are combined with the oxygenator where the impermeable capillaries are cooled/heated by the cooling/heating medium running over them, or in more ancient apparatuses also separate devices where the blood which passed the oxygenator before its return into the patient flows through the filter/exchanger, where it gets in contact with the cooling/heating medium. Purpose of these devices—see e.g. patent EP1623733A2—is to manipulate the temperature of the whole patient, not to precisely adjust the temperature of his blood. The temperature is affected e.g. so that in the process of cooling the patient there is set the temperature of the cooling medium, not that of the blood, and this temperature of the coolant is set by a certain difference lower than the patent's body temperature and the warming up runs analogously. The process is controlled manually by the physician or by a perfusionist.
Blood temperature is also manipulated in patient's whole body hypothermia or in local hypothermia of brain e.g. in states after successful resuscitation in a patient with a sudden cardiac arrest, where such cooling positively affects possible future neurological deficit. For this purpose there may be used e.g. the device described in EP1132101A1, which enables to maintain temperature of the object in the desired level. In this device the blood of the patient is mixed with a cooled solution and afterwards it is concentrated and so the blood temperature is controlled at the instance of its reentrance into the cooled object.
As described, manipulating the blood temperature we can retard the coagulation processes in the blood. Up to the present time the blood temperature in the extracorporeal circuit was not manipulated for the sake to influence coagulation in the extracorporeal circuit. Yet this not employed possibility of anticoagulation activity seems to be very regardful to the patient. There offers itself the following solution: The blood let out of the patient's body, i.e. before it is led into the device substituting the kidney, is cooled and on the output of this device the blood temperature is raised again and the warmed blood is reintroduced in the patient's body.